Annals of Oncology 13:1893-1898, 2002
© 2002 European Society for Medical Oncology
Original Paper |
Phase II study of capecitabine plus cisplatin as first-line chemotherapy in advanced gastric cancer
1 Section of Hematology–Oncology, Department of Medicine and 2 Department of General Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
Received 25 February 2002; revised 22 April 2002; accepted 13 May 2002
 |
Abstract |
|---|
 Top Abstract IntroductionPatients and methodsResultsDiscussionReferences |
|---|
Background:
A phase II study was conducted to assess the efficacy and tolerability of combination therapy with capecitabine and cisplatin in patients with advanced gastric cancer.
Patients and methods:
Patients with previously untreated metastatic or unresectable measurable gastric adenocarcinoma received oral capecitabine 1250 mg/m2 twice daily, days 1–14, and i.v. cisplatin 60 mg/m2 on day 1. This cycle was repeated every 3 weeks.
Results:
Forty-two patients were enrolled in this study. Of these, 38 patients were assessable for efficacy and 40 were assessable for toxicity. One patient achieved a complete response and 22 patients had partial responses, giving an overall response rate of 54.8% in the intention-to-treat population (95% confidence interval 39.8% to 69.8%). The median time to progression was 6.3 months and the median overall survival was 10.1 months. The principal adverse events were neutropenia and hand-foot syndrome. Grade 3/4 adverse events were neutropenia (32.5% of patients), thrombocytopenia (10%), stomatitis (2.5%) and diarrhea (5%). Grade 2 and 3 hand–foot syndrome occurred in 20% and 7.5% of patients, respectively. There were no treatment-related deaths.
Conclusions:
The combination of capecitabine and cisplatin is active and well tolerated in patients with advanced gastric cancer.
Key words: capecitabine, chemotherapy, cisplatin, stomach cancer
|
Introduction |
|---|
|
TopAbstractIntroductionPatients and methodsResultsDiscussionReferences |
|---|
Despite a decreasing trend in the incidence of gastric cancer in nearly all countries, it is still estimated to be the second most common cancer in the world [1], and the most common cancer in Korea [2]. The median survival in patients with advanced gastric cancer (AGC) is 6–9 months in patients receiving chemotherapy. Median survival times of 3 months have been reported in untreated patients in randomized trials from the early 1990s. There is a need for effective systemic therapy to improve the treatment of AGC.
The apparent synergy between 5-fluorouracil (5-FU) and cisplatin has led to the widespread use of regimens combining these agents for various kinds of tumors. In AGC, 5-FU/cisplatin (FP) regimens have shown response rates of >40% in phase II studies [3, 4]. With the majority of FP regimens, 5-FU is administered as a continuous infusion. The promising antitumor activity observed with FP has been confirmed in large-scale, phase III studies. In a phase III trial, an FP regimen produced improved response rates compared with 5-FU, doxorubicin and mitomycin (FAM), or 5-FU monotherapy, although overall survival did not differ between the three groups [5]. Similarly, a trial conducted by the European Organization for the Research and Treatment of Cancer (EORTC) reported that an FP regimen showed a trend towards improved response rates in patients with AGC compared with a combination of 5-FU, doxorubicin and methotrexate (FAMTX) or etoposide, leucovorin and bolus 5-FU (ELF) [6]. Notably, a prospective, randomized phase III trial in patients with advanced esophagogastric cancer demonstrated that the combination of epirubicin, cisplatin and continuous infusion 5-FU (ECF) achieved significantly improved response rates (P = 0.0002) and overall survival (P = 0.0009) compared with FAMTX [7].
A recent study has shown that the addition of biweekly cisplatin to high-dose infusional 5-FU/leucovorin achieves favorable efficacy, including improved overall survival, and a favorable safety profile compared with both infused 5-FU monotherapy and 5-FU/leucovorin (AIO regimen) as first-line therapy in patients with AGC [8]. However, catheters and pumps are necessary for the administration of protracted infusion 5-FU, requiring frequent outpatient visits or admission during which a schedule of short infusions is administered. These factors add to the cost, morbidity and the inconvenience of treatment. The oral 5-FU prodrug, doxifluridine (Furtulon®), which is used in Japan and Korea for the treatment of AGC, has been evaluated in combination with cisplatin in patients with AGC [9, 10]. However, the value of doxifluridine is limited by gastrointestinal side effects. There is, therefore, a need for convenient, well-tolerated alternatives to doxifluridine and i.v. 5-FU.
Capecitabine (N4-pentoxylcarbonyl-5'-deoxy-5-fluorocytidine; Xeloda®; Hoffmann-La Roche Ltd, Basel, Switzerland) is a novel fluoropyrimidine carbamate. As an oral agent that enables chronic dosing, capecitabine mimics continuous infusion 5-FU without the complications and inconvenience associated with central venous access. Capecitabine is absorbed as an intact molecule through the intestinal mucosa, thereby avoiding the gastrointestinal toxicity associated with doxifluridine and other non-selective fluoropyrimidines. In preclinical xenograft models, oral capecitabine was highly active against gastric cancer [11, 12]. Capecitabine is also active in patients with AGC. A phase II study showed that intermittent capecitabine (1657 mg/m2 daily dose for 21 days, followed by a 7-day rest period) achieved tumor responses in six of 25 patients (24%) with previously untreated AGC [13]. Capecitabine in combination with cisplatin produced additive antitumor activity in human gastric cancer xenografts in mice [12, 14]. These findings indicate the feasibility of substituting i.v. 5-FU with capecitabine in fluoropyrimidine/cisplatin therapy for patients with AGC.
Because capecitabine is active as a single agent in AGC, is easy to administer and has a different mechanism of action and toxicity profile from cisplatin, we chose to further explore capecitabine/cisplatin combination treatment in patients with AGC.
|
Patients and methods |
|---|
|
TopAbstractIntroductionPatients and methodsResultsDiscussionReferences |
|---|
Patient selection
Patients were eligible if they had histologically confirmed advanced or metastatic gastric adenocarcinoma with at least one unidimensionally measurable lesion [i.e. with at least one diameter
2 cm, as assessed by physical or X-ray examination including chest X-ray or computed tomography (CT) scan]. Patients were 18 years of age with a performance status of 0–2 on the Eastern Cooperative Oncology Group (ECOG) scale, and had received no prior chemotherapy or radiation therapy. Adequate hematological (hemoglobin 9 g/dl, absolute neutrophil count 2 x 109/l, platelet count 100 x 109/l), hepatic (total bilirubin 
1.5 mg/dl, serum transaminases 3 x upper normal limit or 5 x upper normal limit in cases of hepatic metastases) and renal (serum creatinine 1.5 mg/dl) function were required. Patients with unresolved bowel obstruction or malabsorption syndrome were excluded. The protocol was approved by the institutional review board of the Asan Medical Center, and all patients gave written informed consent before enrolment.
Treatment schedule
Capecitabine was administered orally at a dose of 1250 mg/m2 twice daily according to the standard intermittent schedule (14 days of treatment followed by a 7-day rest period). Cisplatin was administered intravenously at a dose of 60 mg/m2 for 1 h with a standard hydration method on day 1, and repeated every 3 weeks. Ondansetron and dexamethasone were routinely used for the prevention of emesis before the administration of cisplatin. Treatment was continued until disease progression or unacceptable toxicity, or if the patient chose to discontinue treatment.
Dose modification for adverse events
Toxicity was evaluated before each treatment cycle according to the National Cancer Institute Common Toxicity Criteria (NCI CTC), version 2.0. For hand–foot syndrome, the following grading system was used: grade 1, numbness, dysesthesia, painless swelling or erythema not disrupting normal activities; grade 2, painful erythema and/or swelling, or symptoms affecting activities of daily living; and grade 3, moist desquamation, ulceration, blistering, and/or severe pain or symptoms making the patient unable to work or perform the activities of daily living. The capecitabine dose was adjusted for hematological adverse events as follows: (i) for grade 1 neutropenia at day 22, no dose reduction or schedule adjustments were required; (ii) for grade 2 neutropenia or grade 1 thrombocytopenia at day 22, the dose of capecitabine was reduced by 25%; and (iii) for grade 3 neutropenia or grade 2 thrombocytopenia at day 22, the treatment was delayed until resolved to grade 2 neutropenia or grade 1 thrombocytopenia. However, no treatment interruption or dose reduction for anemia was required, and anemia was treated as clinically indicated. The capecitabine dose was adjusted for non-hematological adverse events as outlined in Table 1.
|
Dose adjustment criteria for cisplatin were based on serum creatinine levels immediately prior to each cycle. If serum creatinine was <1.5 mg/dl, full-dose cisplatin was given; if serum creatinine was 1.5–2.5 mg/dl, 50% cisplatin was administered; if serum creatinine was >2.5 mg/dl, the patient was excluded from the study. Patients were required to meet all the following criteria to begin the next cycle of treatment: platelet count
75 x 109/l; neutrophil count 1 x 109/l; resolution or improvement of clinically significant non-hematological adverse events (including diarrhea, mucositis and hand–foot syndrome) to grade 1 or 0. If treatment was delayed for 3 weeks, patients were excluded from the study.
Assessment of compliance and dose intensity
Compliance with capecitabine therapy was monitored by questioning patients and counting their remaining pills at each outpatient visit. The ratio of the actual administered dose to the scheduled dose was calculated. Dose intensity was defined as the total amount of drug given (mg/m2) divided by the number of weeks.
Pretreatment, follow-up studies and response evaluation
Physical examination and chest X-rays were carried out before each cycle of therapy. Complete blood counts were performed weekly and biochemical tests were performed on days 15 of each cycle. Tumors were measured every three cycles until the tumor progressed. Tumor response was classified on the basis of the response evaluation criteria in solid tumors (RECIST) guidelines [15]: complete response (CR), the disappearance of all target lesions; partial response (PR), a decrease of at least 30% in the sum of the longest diameters of target lesions; progressive disease (PD), an increase of at least 20% in the sum of the longest diameters of target lesions or the appearance of one or more new lesions; stable disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Patients with CR or PR required a confirmatory disease assessment at least 4 weeks later. Patients with no confirmed tumor response were not regarded as responders.
Statistical analysis
All enrolled patients were included in the intention-to-treat analysis of efficacy. The trial was conducted according to the two-stage Gehan design [16] with response rate as the primary end-point. We planned to enroll at least 30 assessable patients, with a target minimum response of 30%. If no objective tumor responses were seen among the first nine assessable patients in the study, then the probability of a response rate 30% would be <5%, and the study would be discontinued. One or more responses would indicate that continuation was warranted, and 
30 patients would be required to estimate the 95% confidence interval (CI) for the true response rate with a maximum width of 36%. However, the number of patients enrolled was increased to 42 patients to better estimate the response rate. Time to progression (TTP), survival and duration of response were estimated as secondary end-points by the Kaplan–Meier method. The duration of response was defined as the interval from the onset of CR or PR (whichever status was recorded first) until evidence of PD was found; TTP was calculated from the date of entry to the study to the date of PD; overall survival was measured from the date of entry to the date of last follow-up or death.
|
Results |
|---|
|
TopAbstractIntroductionPatients and methodsResultsDiscussionReferences |
|---|
Patient characteristics
A total of 42 patients were enrolled from March 2000 to June 2001. The characteristics of the patients are listed in Table 2. The median age was 51.5 years, and most of the patients (92.8%) had a good performance status (ECOG 0 or 1). Tumors were metastatic in 37 (88.1%) patients and locally advanced in 5 (11.9%) patients. The liver and lymph nodes were the most common sites of metastases. Four patients (9.5%) had a history of prior surgery, but no patient had received prior chemotherapy or radiotherapy.
|
Efficacy and survival
A total of 38 patients were assessable for response (Table 3). The remaining four patients were not assessable for response because of loss to follow-up. One CR confirmed by endoscopic biopsy and 22 confirmed PRs were observed, giving an overall response rate of 54.8% (23 of 42) (95% CI 39.8% to 69.8%) in the intention-to-treat population. All five patients with locally advanced disease achieved a PR. After an excellent response to protocol therapy, surgery was attempted in two patients, although complete resection was not achieved. The median follow-up period was 18.2 months (range 16.2–20.8 months). The median duration of response in the 23 responding patients was 6.2 months (range 2.4–9.9 months). The median TTP for all patients was 6.3 months (range 4– 8.7 months) (Figure 1). The median overall survival was 10.1 months (range 7–13.1 months) (Figure 2), with a 1-year survival rate of 45.8% (95% CI 30.7% to 60.9%).
|
|
|
Adverse events
A total of 216 treatment cycles (median 5, range 1–11 cycles) were administered, of which 212 were administered to the 40 patients assessable for safety. The frequencies of hematological and non-hematological adverse events are shown in Tables 4 and 5, respectively. The most common hematological adverse event was neutropenia, which occurred with grade 3/4 intensity in 13 patients (32.5%) and in 38 cycles (17.9%); however, no patient experienced febrile neutropenia. Although grade 3/4 thrombocytopenia was observed in four patients (10%), with only one patient experiencing grade 4, and in six cycles (2.8%), no patients required platelet transfusions. Hand–foot syndrome was also relatively common, with grades 2 and 3 occurring in eight (20%) and three (7.5%) patients, respectively. There were no treatment-related deaths.
|
|
Treatment was delayed or the dose was reduced in 89 cycles. Doses were reduced in 75 cycles (34.7%) for the following reasons: hematological toxicity (21.8%); nausea/vomiting (6.5%); hand–foot syndrome (6%); and diarrhea (0.5%). Treatment was delayed in 38 cycles (17.6%). Therefore, the median dose intensity for capecitabine over all treatment cycles was 10 290 mg/m2/week (range 6496–11 666 mg/m2/week) and that of cisplatin was 18.6 mg/m2/week (range 13.6–20 mg/m2/week), which correspond to 87% and 93.1% of the planned dose intensities, respectively. Compliance with the treatment regimen was good, with 97.1% compliance during the first three cycles for capecitabine.
|
Discussion |
|---|
|
TopAbstractIntroductionPatients and methodsResultsDiscussionReferences |
|---|
The present study shows that the combination of capecitabine and cisplatin is active and tolerable as first-line chemotherapy for AGC. The advantage of the high single-agent activity and favorable safety profile of capecitabine was clearly demonstrated in two recent large, phase III studies comparing capecitabine with bolus 5-FU plus leucovorin (Mayo Clinic regimen) as first-line therapy for metastatic colorectal cancer [17, 18].
Capecitabine has been previously shown to be active in AGC, achieving a response rate of 24% with a favorable safety profile in patients with previously untreated AGC [13]. Because the safety profile of capecitabine differs from that of cisplatin, with little overlap of key side effects, we used the standard, intermittent capecitabine regimen 1250 mg/m2 twice daily for 14 days followed by a 7-day rest period with cisplatin 60 mg/m2 on day 1 every 21 days. Cisplatin was administered at a relatively lower dose intensity compared with many previously reported regimens so as not to decrease the compliance with capecitabine. The capecitabine/cisplatin regimen demonstrated promising efficacy, with tumor response rates (54.8%), median TTP (6.3 months) and median overall survival (10.1 months) comparing favorably with the reported efficacy of high-dose infusional 5-FU/cisplatin and other combination chemotherapies. High-dose, infusional 5-FU/cisplatin regimen was reported to achieve a response rate of 37%, median progression-free survival of 6 months and median overall survival of 9.7 months [8]. The main side effect associated with the capecitabine/cisplatin regimen was neutropenia, which occurs only rarely with single-agent capecitabine [17, 18]. Therefore, the incidence of this side-effect with the combination may be attributable to cisplatin. Nevertheless, neutropenia was an isolated event, was not associated with fever or infection and did not lead to the administration of a reduced dose intensity. Complete blood counts were routinely assessed weekly, which may have detected a higher incidence of neutropenia compared with other studies. The capecitabine/cisplatin regimen in this study showed modest toxicity. An explanation for the relatively modest toxicity could be the dose of cisplatin used (60 mg/m2 every 21 days). Cisplatin was administered at a relatively lower dose intensity compared with many previously reported regimens.
Compliance can be an issue with oral chemotherapy. If a self-administered drug is combined with a highly emetogenic agent, such as cisplatin, lack of compliance may compromise treatment. However, anti-emetic treatment comprising ondansetron and dexamethasone was routinely administered prior to the infusion of cisplatin during this study, and compliance was high. Grade 3/4 emesis occurred in only 10% of patients and 2.3% of cycles, which is near optimal for cisplatin administration. Compliance for capecitabine was maintained at 97.1% for the first three cycles, and 87% of the projected dose intensity of capecitabine was administered throughout treatment.
In conclusion, capecitabine plus cisplatin is safe and effective as first-line treatment for AGC. This regimen can be administered on an outpatient basis and is more convenient for patients than regimens combining infusional 5-FU with cisplatin.
The results of the current study confirm the potential of capecitabine to replace protracted infusion 5-FU in regimens used in the treatment of AGC. Based upon the promising results observed in this study, further evaluation of capecitabine plus cisplatin in a randomized, phase III trial is planned.
|
Acknowledgements |
|---|
This work was presented at the Thirty-seventh Annual Meeting of the American Society of Clinical Oncology, San Francisco, CA, May 12–15, 2001.
|
Footnotes |
|---|
+ Correspondence to: Dr Y. K. Kang, Section of Hematology-Oncology, Department of Medicine, Asan Medical Center, 388-1 Poongnap-dong, Songpa-ku, Seoul, Korea 138-736. Tel: +82-2-3010-3210; Fax: +82-2-3010-6961; E-mail: ykkang{at}amc.seoul.kr
|
References |
|---|
|
TopAbstractIntroductionPatients and methodsResultsDiscussionReferences |
|---|
1. Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of eighteen major cancers in 1985. Int J Cancer 1993; 54: 594–606.[Web of Science][Medline]
2. Suh CI, Suh KE, Park SH et al. Annual report of the central cancer registry in Korea—1998 (based on registered data from 124 hospitals). J Korean Cancer Assoc 2000; 32: 827–834.
3. Lacave AJ, Baron FJ, Anton LM et al. Combination chemotherapy with cisplatin and 5-fluorouracil 5-day infusion in the therapy of advanced gastric cancer: a phase II trial. Ann Oncol 1991; 2: 751–754.
4. Rougier P, Ducreux M, Mahjoubi M et al. Efficacy of combined 5-fluorouracil and cisplatinum in advanced gastric carcinomas. A phase II trial with prognostic factor analysis. Eur J Cancer 1994; 30A: 1263–1269.[Web of Science][Medline]
5. Kim NK, Park YS, Heo DS et al. A phase III randomized study of 5-fluorouracil and cisplatin versus 5-fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil alone in the treatment of advanced gastric cancer. Cancer 1993; 71: 3813–3818.[Web of Science][Medline]
6. Vanhoefer U, Rougier P, Wilke H et al. Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol 2000; 18: 2648–2657.
7. Webb A, Cunningham D, Scarffe JH et al. Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 1997; 15: 261–267.
8. Vanhoefer U, Wagner T, Lutz M et al. Randomized phase II study of weekly 24-h infusion of high dose 5-FU ± fonilic acid (HD-FU ± FA) versus HD-FU/FA/biweekly cisplatin in advanced gastric cancer. EORTC-trial 40953. Eur J Cancer 2001; 37: 27.
9. Koizumi W, Kurihara M, Sasai T et al. A phase II study of combination therapy with 5'-deoxy-5-fluorouridine and cisplatin in the treatment of advanced gastric cancer with primary foci. Cancer 1993; 72: 658–662.[Web of Science][Medline]
10. Ahn MJ, Han DS, Sohn JH et al. Combination chemotherapy of oral 5'-deoxy-5-fluorouridine and cisplatin in advanced gastric cancer: a phase II study. J Korean Med Sci 1998; 13: 612–616.[Medline]
11. Ishikawa T, Sekiguchi F, Fukase Y et al. Positive correlation between the efficacy of capecitabine and doxifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumors in human cancer xenografts. Cancer Res 1998; 58: 685–690.
12. Ishitsuka H. Capecitabine: preclinical pharmacology studies. Invest New Drugs 2000; 18: 343–354.[Web of Science][Medline]
13. Koizumi W, Taguchi T. A phase II study of capecitabine (Xeloda) in patients with advanced/metastatic gastric carcinoma. Proc Am Soc Clin Oncol 2001; 20: 142b (Abstr 2320).
14. Verweij J. Rational design of new tumoractivated cytotoxic agents. Oncology 1999; 57: S9–S15.
15. Therasse P, Arbuck SG, Eisenhauer EA et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000; 92: 205–216.
16. Gehan EA. The determination of the number of patients required in a preliminary and follow-up trial of a new chemotherapeutic agent. J Chronic Dis 1961; 13: 346–353.[Web of Science][Medline]
17. Hoff PM, Ansari R, Batist G et al. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol 2001; 19: 2282–2292.
18. Van Cutsem E, Twelves C, Cassidy J et al. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol 2001; 19: 4097–4106.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. F. C. Okines, A. R. Norman, P. McCloud, Y.-K. Kang, and D. Cunningham Meta-analysis of the REAL-2 and ML17032 trials: evaluating capecitabine-based combination chemotherapy and infused 5-fluorouracil-based combination chemotherapy for the treatment of advanced oesophago-gastric cancer Ann. Onc., September 1, 2009; 20(9): 1529 - 1534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Moehler, S. Kanzler, M. Geissler, J. Raedle, M. P. Ebert, S. Daum, D. Flieger, T. Seufferlein, P. R. Galle, T. Hoehler, et al. A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction Ann. Onc., July 15, 2009; (2009) mdp269v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-K. Kang, W.-K. Kang, D.-B. Shin, J. Chen, J. Xiong, J. Wang, M. Lichinitser, Z. Guan, R. Khasanov, L. Zheng, et al. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial Ann. Onc., April 1, 2009; 20(4): 666 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-C. Jo, J.-L. Lee, M.-H. Ryu, S. J. Sym, S. S. Lee, H. M. Chang, T. W. Kim, J. S. Lee, and Y.-K. Kang Docetaxel Monotherapy as a Second-line Treatment after Failure of Fluoropyrimidine and Platinum in Advanced Gastric Cancer: Experience of 154 Patients with Prognostic Factor Analysis Jpn. J. Clin. Oncol., December 1, 2007; 37(12): 936 - 941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Lee, S.-B. Kim, S.-I. Park, Y. H. Kim, J.-S. Ryu, H.-Y. Song, J. H. Shin, H. Y. Jung, G. H. Lee, K. D. Choi, et al. Capecitabine and Cisplatin Chemotherapy (XP) Alone or Sequentially Combined Chemoradiotherapy Containing XP Regimen in Patients with Three Different Settings of Stage IV Esophageal Cancer Jpn. J. Clin. Oncol., November 1, 2007; 37(11): 829 - 835. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ohtsu, S. Yoshida, and N. Saijo Disparities in Gastric Cancer Chemotherapy Between the East and West J. Clin. Oncol., May 10, 2006; 24(14): 2188 - 2196. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Ajani Evolving Chemotherapy for Advanced Gastric Cancer Oncologist, October 1, 2005; 10(suppl_3): 49 - 58. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Fakih, P. J. Creaven, N. Ramnath, D. Trump, M. Javle, S. Strychor, T. V.W. Repinski, B. A. Zamboni, J. K. Schwarz, R. A. French, et al. Phase I and Pharmacokinetic Study of Weekly Docetaxel, Cisplatin, and Daily Capecitabine in Patients with Advanced Solid Tumors Clin. Cancer Res., August 15, 2005; 11(16): 5942 - 5949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Wohrer, M. Raderer, and M. Hejna Palliative chemotherapy for advanced gastric cancer Ann. Onc., November 1, 2004; 15(11): 1585 - 1595. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Undevia, H. L. Kindler, L. Janisch, S. C. Olson, R. L. Schilsky, N. J. Vogelzang, K. A. Kimmel, T. A. Macek, and M. J. Ratain A phase I study of the oral combination of CI-994, a putative histone deacetylase inhibitor, and capecitabine Ann. Onc., November 1, 2004; 15(11): 1705 - 1711. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. S. Heo, H. M. Chang, T. W. Kim, M.-H. Ryu, J.-H. Ahn, S. B. Kim, J. S. Lee, W. K. Kim, H. K. Cho, and Y.-K. Kang Hand-Foot Syndrome in Patients Treated With Capecitabine-Containing Combination Chemotherapy J. Clin. Pharmacol., October 1, 2004; 44(10): 1166 - 1172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Pivot, E. Chamorey, E. Guardiola, N. Magne, A. Thyss, J. Otto, B. Giroux, Z. Mouri, M. Schneider, and G. Milano Phase I and pharmacokinetic study of the association of capecitabine-cisplatin in head and neck cancer patients Ann. Onc., October 1, 2003; 14(10): 1578 - 1586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. W. Kim, H. M. Chang, H. J. Kang, J. R. Lee, M. H. Ryu, J. H. Ahn, J. H. Kim, J. S. Lee, and Y. K. Kang Phase II study of capecitabine plus cisplatin as first-line chemotherapy in advanced biliary cancer Ann. Onc., July 1, 2003; 14(7): 1115 - 1120. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||